The objective of this proposal is to develop a new antimicrobial drug which is effective in the treatment of infections caused by multiantibiotic-resistant (MAR) Gram+ (G+) bacteria. The strategy targets the replication specific G+ DNA polymerase III (pol III) enzyme as a novel target with G+ polIII- specific inhibitors based on 6-anilinopyridine (AP), as novel, target specific agents. The Phase I research plan addresses: 1.) specific chemical modification of two potent AP prototypes 6-(3-ethyl-4-methylanilino) uracil (EMAU) and 6-(3-ethyl-4-methylanilino)isocytosine (EMAiCyt). 2). a combinatorial chemistry program to generate drug candidates from the AP prototypes, and 3.) in-vitro antibacterial and biochemical assessment of the resulting products to identify candidates with enhanced clinical potential. The Phase II plan will examine the most promising candidates from Phase I with respect to basic pharmacology and toxicology in animals as well as evaluation in a relevant mouse infection model. PROPOSED COMMERCIAL APPLICATION: Proposed commercial application not available.